This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Biomedical assays built around affinity sensing have achieved great success in immunoassays, gene-profiling, transcription factor studies and drug discovery. Yet affinity assays have an Achilles'heel [unreadable]positive signal relies entirely on the design, engineering, and prior verification of the probe-target interaction. This restricts affinity assays to a subset of biosensing where the target is known a priori, with the goal to measure the amount of target in the sample for detection, diagnosis, or therapy. Discovery, especially biomarker discovery, is not possible with affinity arrays, so the technological advancements of high throughput, label-free, and high sensitivity have not been widely applied to discovery. We are working seed project to develop the technology to couple the quantified, high-throughput label-free microarray platform of Spectral Reflectance Biosensing (SRB) developed at BU to mass spectrometry to demonstrate quantified, high-throughput biomarker discovery. During the development of the technique, we expect to design and optimize protocols for direct verification of the SRB system for existing applications and to develop new applications as the technology is evaluated and optimized. Initial MALDI-TOF MS analyses seem promising. Internal university funding has been obtained to support the initial stages of the work.